Nanoparticle-Catalyzed Transamination under Tumor Microenvironment Conditions: A Novel Tool to Disrupt the Pool of Amino Acids and GSSG in Cancer Cells.

Catalytic cancer therapy targets cancer cells by exploiting the specific characteristics of the tumor microenvironment (TME). TME-based catalytic strategies rely on the use of molecules already present in the TME. Amino groups seem to be a suitable target, given the abundance of proteins and peptides in biological environments. Here we show that catalytic CuFe2O4 nanoparticles are able to foster transaminations with different amino acids and pyruvate, another key molecule present in the TME. We observed a significant in cellulo decrease in glutamine and alanine levels up to 48 h after treatment. In addition, we found that di- and tripeptides also undergo catalytic transamination, thereby extending the range of the effects to other molecules such as glutathione disulfide (GSSG). Mechanistic calculations for GSSG transamination revealed the formation of an imine between the oxo group of pyruvate and the free -NH2 group of GSSG. Our results highlight transamination as alternative to the existing toolbox of catalytic therapies.

Small Warriors of Nature: Novel Red Emissive Chlorophyllin Carbon Dots Harnessing Fenton-Fueled Ferroptosis for In Vitro and In Vivo Cancer Treatment.

The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin-based carbon dots (Chl-D CDs) are successfully synthesized. Chl-D CDs exhibit unique spectroscopic traits and are found to induce a Fenton-like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl-D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl-D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl-D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl-D CDs' anticancer activity. Notably, the Chl-D CDs' capacity to trigger a Fenton-like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl-CDs can lead to a secure and efficient combined cancer therapy.

In Cellulo Bioorthogonal Catalysis by Encapsulated AuPd Nanoalloys: Overcoming Intracellular Deactivation.

Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed AuPd nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media. We also show that the intracellular catalytic performance of these nanoalloys is significantly enhanced by protecting them following two different encapsulation methods. Encapsulation in mesoporous silica nanorods resulted in augmented catalyst reactivity, whereas the use of a biodegradable PLGA matrix increased nanoalloy delivery across the cell membrane. The functional potential of encapsulated AuPd was demonstrated by releasing the potent chemotherapy drug paclitaxel inside cancer cells. Nanoalloy encapsulation provides a novel methodology to develop nanoreactors capable of mediating new-to-life reactions in cells.

Platinum nanoplatforms: classic catalysts claiming a prominent role in cancer therapy.

Platinum nanoparticles (Pt NPs) have a well-established role as a classic heterogeneous catalyst. Also, Pt has traditionally been employed as a component of organometallic drug formulations for chemotherapy. However, a new role in cancer therapy is emerging thanks to its outstanding catalytic properties, enabling novel approaches that are surveyed in this review. Herein, we critically discuss results already obtained and attempt to ascertain future perspectives for Pt NPs as catalysts able to modify key processes taking place in the tumour microenvironment (TME). In addition, we explore relevant parameters affecting the cytotoxicity, biodistribution and clearance of Pt nanosystems. We also analyze pros and cons in terms of biocompatibility and potential synergies that emerge from combining the catalytic capabilities of Pt with other agents such as co-catalysts, external energy sources (near-infrared light, X-ray, electric currents) and conventional therapies.

Upconverting Carbon Nanodots from Ethylenediaminetetraacetic Acid (EDTA) as Near-Infrared Activated Phototheranostic Agents.

This work describes the synthesis of nitrogen-doped carbon nanodots (CNDs) synthesized from ethylenediaminetetraacetic acid (EDTA) as a precursor and their application as luminescent agents with a dual-mode theranostic role as near-infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized by tumor cells and exhibit very limited cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for phototheranostic purposes, for example, simultaneous imaging and therapy can be carried out on cancer cells by using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs, NIR remote activation induces the in vitro killing of U251MG cells. Through the use of flow imaging cytometry, we have been able to successfully map and quantify the different types of cell deaths induced by the presence of intracellular superoxide anions (. O2 - ) and hydrogen peroxide (H2 O2 ) ROS generated in situ upon NIR irradiation.

Nitrogen-Induced Transformation of Vitamin†C into Multifunctional Up-converting Carbon Nanodots in the Visible-NIR Range.

Water-soluble, biocompatible, and photoluminescent carbon nanodots have been obtained from the rationalized carbonization of vitamin C, a well-known antioxidant molecule in the presence of an amine co-reactant. Herein, we describe the positive influence of N-doping to induce a unique pH-dependent lifetime decay response that would be potentially attractive in biological backgrounds with intrinsic fluorescence fluctuations. In addition, the selectivity and sensitivity of the N-containing carbon nanoprobes towards the detection of copper ions at ppm levels is critically enhanced in comparison with the un-doped counterpart, especially in the near-infrared (NIR) range. Finally, the up-converting properties have been also successfully applied to image tumor cells in the visible range and remarkably, in the NIR region in which minimal tissue or water absorption and maximum penetration depth are expected.

A Nanoarchitecture Based on Silver and Copper Oxide with an Exceptional Response in the Chlorine-Promoted Epoxidation of Ethylene.

The selective oxidation of ethylene to ethylene epoxide is highly challenging as a result of competing reaction pathways leading to the deep oxidation of both ethylene and ethylene oxide. Herein we present a novel catalyst based on silver and copper oxide with an excellent response in the selective oxidation pathway towards ethylene epoxide. The catalyst is composed of different silver nanostructures dispersed on a tubular copper oxide matrix. This type of hybrid nanoarchitecture seems to facilitate the accommodation of chlorine promoters, leading to high yields at low reaction temperatures. The stability after the addition of chlorine promoters implies a substantial improvement over the industrial practice: a single pretreatment step at ambient pressure suffices in contrast with the common practice of continuously feeding organochlorinated precursors during the reaction.

Nanomedicine Targeting Cuproplasia in Cancer: Labile Copper Sequestration Using Polydopamine Particles Blocks Tumor Growth In Vivo through Altering Metabolism and Redox Homeostasis.

Copper plays critical roles as a metal active site cofactor and metalloallosteric signal for enzymes involved in cell proliferation and metabolism, making it an attractive target for cancer therapy. In this study, we investigated the efficacy of polydopamine nanoparticles (PDA NPs), classically applied for metal removal from water, as a therapeutic strategy for depleting intracellular labile copper pools in triple-negative breast cancer models through the metal-chelating groups present on the PDA surface. By using the activity-based sensing probe FCP-1, we could track the PDA-induced labile copper depletion while leaving total copper levels unchanged and link it to the selective MDA-MB-231 cell death. Further mechanistic investigations revealed that PDA NPs increased reactive oxygen species (ROS) levels, potentially through the inactivation of superoxide dismutase 1 (SOD1), a copper-dependent antioxidant enzyme. Additionally, PDA NPs were found to interact with the mitochondrial membrane, resulting in an increase in the mitochondrial membrane potential, which may contribute to enhanced ROS production. We employed an in vivo tumor model to validate the therapeutic efficacy of PDA NPs. Remarkably, in the absence of any additional treatment, the presence of PDA NPs alone led to a significant reduction in tumor volume by a factor of 1.66 after 22 days of tumor growth. Our findings highlight the potential of PDA NPs as a promising therapeutic approach for selectively targeting cancer by modulating copper levels and inducing oxidative stress, leading to tumor growth inhibition as shown in these triple-negative breast cancer models.

Heterogeneous-Driven Glutathione Oxidation: Defining the Catalytic Role of Chalcopyrite Nanoparticles.

Transition-metal nanocatalysis represents a novel alternative currently experiencing flourishing progress to tackle the tumor microenvironment (TME) in cancer therapy. These nanomaterials aim at attacking tumor cells using the intrinsic selectivity of inorganic catalysts. In addition, special attention to tune and control the release of these transition metals is also required. Understanding the chemical reactions behind the catalytic action of the transition-metal nanocatalysts and preventing potential undesired side reactions caused by acute cytotoxicity of the released ionic species represent another important field of research. Specifically, copper-based oxides may suffer from acute leaching that potentially may induce toxicity not only to target cancer cells but also to nearby cells and tissues. In this work, we propose the synthesis of chalcopyrite (CuFeS2) nanostructures capable of triggering two key reactions for an effective chemodynamic therapy (CDT) in the heterogeneous phase: (i) glutathione (GSH) oxidation and (ii) oxidation of organic substrates using H2O2, with negligible leaching of metals under TME-like conditions. This represents an appealing alternative toward the development of safer copper-iron-based nanocatalytic materials with an active catalytic response without incurring leaching side phenomena.

Platinum-based nanodendrites as glucose oxidase-mimicking surrogates.

Catalytic conversion of glucose represents an interesting field of research with multiple applications. From the biotechnology point of view, glucose conversion leads to the fabrication of different added-value by-products. In the field of nanocatalytic medicine, the reduction of glucose levels within the tumor microenvironment (TME) represents an appealing approach based on the starvation of cancer cells. Glucose typically achieves high conversion rates with the aid of glucose oxidase (GOx) enzymes or by fermentation. GOx is subjected to degradation, possesses poor recyclability and operates under very specific reaction conditions. Gold-based materials have been typically explored as inorganic catalytic alternatives to GOx in order to convert glucose into building block chemicals of interest. Still, the lack of sufficient selectivity towards certain products such as gluconolactone, the requirement of high fluxes of oxygen or the critical size dependency hinder their full potential, especially in liquid phase reactions. The present work describes the synthesis of platinum-based nanodendrites as novel enzyme-mimicking inorganic surrogates able to convert glucose into gluconolactone with outstanding selectivity values above 85%. We have also studied the enzymatic behavior of these Pt-based nanozymes using the Michaelis-Menten and Lineweaver-Burk models and used the main calculation approaches available in the literature to determine highly competitive glucose turnover rates for Pt or Pt-Au nanodendrites.

Optical Binding-Driven Micropatterning and Photosculpting with Silver Nanorods.

Controlling the nano- and micropatterning of metal structures is an important requirement for various technological applications in photonics and biosensing. This work presents a method for controllably creating silver micropatterns by laser-induced photosculpting. Photosculpting is driven by plasmonic interactions between pulsed laser radiation and silver nanorods (AgNRs) in aqueous suspension; this process leads to optical binding forces transporting the AgNRs in the surroundings, while electronic thermalization results in photooxidation, melting, and ripening of the AgNRs into well-defined 3D structures. This work call these structures Airy castles due to their structural similarity with a diffraction-limited Airy disk. The photosculpted Airy castles contain emissive Ag nanoclusters, allowing for the visualization and examination of the aggregation process using luminescence microscopy. This work comprehensively examines the factors that define the photosculpting process, namely, the concentration and shape of the AgNRs, as well as the energy, power, and repetition rate of the laser. Finally, this work investigates the potential applications by measuring the metal-enhanced luminescence of a europium-based luminophore using Airy castles.

Unravelling the key factors in the chlorine-promoted epoxidation of ethylene over a silver-copper oxide nanocatalyst.

Ethylene oxide is one of the most important raw materials in the chemical industry, with an annual production close to 35 million metric tons. Despite its importance, to date, no metal has been found that can compete with the original silver bulk material catalyst discovered in 1931. Recently, a few copper and copper-silver based nanostructures have demonstrated remarkable selectivity and activity, especially when coupled with an industrial chlorine promoter. The present work evaluates the mechanistic role of chlorine as an active promoter of the selective oxidation of ethylene to ethylene oxide in the presence of a silver-copper oxide hybrid nanocatalyst (AgCuO). Experimental kinetic studies combined with density functional theory (DFT) calculations provide insight into the influence that Ag/CuO-supported chlorine atoms have over the ethylene epoxidation reaction. Remarkably, the typically described indirect route via the formation of an oxametallacycle (OMC) is also accompanied by a direct route. Furthermore, the presence of chlorine seems to facilitate a more favorable adsorption energy for ethylene oxide (EO) than for acetaldehyde (AA), the main reaction by-product. As a result, complete oxidation of EO can be further prevented in the presence of this AgCuO hybrid heteronanostructure.

Gold-Platinum Nanoparticles with Core-Shell Configuration as Efficient Oxidase-like Nanosensors for Glutathione Detection.

Nanozymes, defined as nanomaterials that can mimic the catalytic activity of natural enzymes, have been widely used to develop analytical tools for biosensing. In this regard, the monitoring of glutathione (GSH), a key antioxidant biomolecule intervening in the regulation of the oxidative stress level of cells or related with Parkinson's or mitochondrial diseases can be of great interest from the biomedical point of view. In this work, we have synthetized a gold-platinum Au@Pt nanoparticle with core-shell configuration exhibiting a remarkable oxidase-like mimicking activity towards the substrates 3,3',5,5'-tetramethylbenzidine (TMB) and o-phenylenediamine (OPD). The presence of a thiol group (-SH) in the chemical structure of GSH can bind to the Au@Pt nanozyme surface to hamper the activation of O2 and reducing its oxidase-like activity as a function of the concentration of GSH. Herein, we exploit the loss of activity to develop an analytical methodology able to detect and quantify GSH up to µM levels. The system composed by Au@Pt and TMB demonstrates a good linear range between 0.1-1.0 µM to detect GSH levels with a limit of detection (LoD) of 34 nM.

Unveiling the interplay between homogeneous and heterogeneous catalytic mechanisms in copper-iron nanoparticles working under chemically relevant tumour conditions.

The present work sheds light on a generally overlooked issue in the emerging field of bio-orthogonal catalysis within tumour microenvironments (TMEs): the interplay between homogeneous and heterogeneous catalytic processes. In most cases, previous works dealing with nanoparticle-based catalysis in the TME focus on the effects obtained (e.g. tumour cell death) and attribute the results to heterogeneous processes alone. The specific mechanisms are rarely substantiated and, furthermore, the possibility of a significant contribution of homogeneous processes by leached species - and the complexes that they may form with biomolecules - is neither contemplated nor pursued. Herein, we have designed a bimetallic catalyst nanoparticle containing Cu and Fe species and we have been able to describe the whole picture in a more complex scenario where both homogeneous and heterogeneous processes are coupled and fostered under TME relevant chemical conditions. We investigate the preferential leaching of Cu ions in the presence of a TME overexpressed biomolecule such as glutathione (GSH). We demonstrate that these homogeneous processes initiated by the released by Cu-GSH interactions are in fact responsible for the greater part of the cell death effects found (GSH, a scavenger of reactive oxygen species, is depleted and highly active superoxide anions are generated in the same catalytic cycle). The remaining solid CuFe nanoparticle becomes an active catalyst to supply oxygen from oxygen reduced species, such as superoxide anions (by-product from GSH oxidation) and hydrogen peroxide, another species that is enriched in the TME. This activity is essential to sustain the homogeneous catalytic cycle in the oxygen-deprived tumour microenvironment. The combined heterogeneous-homogeneous mechanisms revealed themselves as highly efficient in selectively killing cancer cells, due to their higher GSH levels compared to healthy cell lines.

Glutathione-Triggered catalytic response of Copper-Iron mixed oxide Nanoparticles. Leveraging tumor microenvironment conditions for chemodynamic therapy.

Heterogeneous catalysis has emerged as a promising alternative for the development of new cancer therapies. In addition, regarding the tumor microenvironment as a reactor with very specific chemical features has provided a new perspective in the search for catalytic nanoarchitectures with specific action against chemical species playing a key role in tumor metabolism. One of these species is glutathione (GSH), whose depletion is the cornerstone of emerging strategies in oncology, since this metabolite plays a pivotal regulatory role as antioxidant agent, dampening the harmful effects of intracellular reactive oxidative species (ROS). Herein, we present copper-iron oxide spinel nanoparticles that exhibit a versatile and selective catalytic response to reduce GSH levels while generating ROS in a cascade reaction. We demonstrate a clear correlation between GSH depletion and apoptotic cell death in tumor cells in the presence of the copper-iron nanocatalyst. Furthermore, we also provide a novel analytical protocol, alternative to state-of-the-art commercial kits, to accurately monitoring the concentration of GSH intracellular levels in both tumor and healthy cells. We observe a selective action of the nanoparticles, with lower toxicity in healthy cell lines, whose intrinsic GSH levels are lower, and intense apoptosis in tumor cells accompanied by a fast reduction of GSH levels.

Hydrophobic gold nanoparticle self-assembly with phosphatidylcholine lipid: membrane-loaded and janus vesicles.

Hybrids of hydrophobic sub-2-nm-diameter dodecanethiol-coated Au nanoparticles and phosphatidylcholine (PC) lipid vesicles made by extrusion were examined by cryogenic transmission electron microscopy (cryoTEM). The nanoparticles loaded the vesicles as a dense monolayer in the hydrophobic core of the lipid bilayer, without disrupting their structure. Nanoparticle-vesicle hybrids could also be made by a dialysis process, mixing preformed vesicles with detergent-stabilized nanoparticles, but this approach led to vesicles only partially loaded with nanoparticles that segregated into hemispherical domains, forming a Janus vesicle-nanoparticle hybrid structure.

LED-driven controlled deposition of Ni onto TiO2 for visible-light expanded conversion of carbon dioxide into C1-C2 alkanes.

Photocatalytic gas-phase hydrogenation of CO2 into alkanes was achieved over TiO2-supported Ni nanoparticles under LED irradiation at 365 nm, 460 nm and white light. The photocatalysts were prepared using photo-assisted deposition of Ni salts under LED irradiation at 365 nm onto TiO2 P25 nanoparticles in methanol as a hole scavenger. This procedure yielded 2 nm Ni particles decorating the surface of TiO2 with a nickel mass content of about 2%. Before the photocatalytic runs, Ni/TiO2 was submitted to thermal reduction at 400 °C in a 10% H2 atmosphere which induced O-defective TiO2-x substrates. The formation of oxygen vacancies, Ti3+ centers and metallic Ni sites upon photocatalytic CO2 hydrogenation was confirmed by operando EPR analysis. In situ XPS under reaction conditions suggested a strong metal-support interaction and the co-existence of zero and divalent Ni states. These photoactive species enhanced the photo-assisted reduction of CO2 below 300 °C to yield CO, CH4 and C2H6 as final products.

Alkyl passivation and amphiphilic polymer coating of silicon nanocrystals for diagnostic imaging.

A method to produce biocompatible polymer-coated silicon nanocrystals for medical imaging is shown. Silica-embedded Si nanocrystals are formed by HSQ thermolysis. The nanocrystals are then liberated from the oxide and terminated with Si-H bonds by HF etching, followed by alkyl monolayer passivation by thermal hydrosilylation. The Si nanocrystals have an average diameter of 2.1 nm ± 0.6 nm and photoluminesce with a peak emission wavelength of 650 nm, which lies within the transmission window of 650-900 nm that is useful for biological imaging. The hydrophobic Si nanocrystals are then coated with an amphiphilic polymer for dispersion in aqueous media with the pH ranging between 7 and 10 and an ionic strength between 30 mM and 2 M, while maintaining a bright and stable photoluminescence and a hydrodynamic radius of only 20 nm. Fluorescence imaging of polymer-coated Si nanocrystals in biological tissue is demonstrated, showing the potential for in vivo imaging.

Evaluation of different dielectric barrier discharge plasma configurations as an alternative technology for green C1 chemistry in the carbon dioxide reforming of methane and the direct decomposition of methanol.

Carbon dioxide reforming of methane and direct decomposition of methanol have been investigated using dielectric barrier discharges (DBD) at atmospheric pressure and reduced working temperatures. Two different plasma reactor configurations are compared and special attention is paid to the influence of the surface roughness of the electrodes on the conversion yields in the first plasma device. The influence of different filling gap dielectric materials (i.e., Al(2)O(3) or BaTiO(3)) in the second packed configuration has been also evaluated. Depending on the experimental conditions of applied voltage, residence time of reactants, feed ratios, or reactor configuration, different conversion yields are achieved ranging from 20 to 80% in the case of methane and 7-45% for the carbon dioxide. The direct decomposition of methanol reaches 60-100% under similar experimental conditions. Interestingly, the selectivity toward the production of hydrogen and carbon monoxide is kept almost constant under all the experimental conditions, and the formation of longer hydrocarbon chains or coke as a byproduct is not detected. The maximum efficiency yields are observed for the packed-bed reactor configuration containing alumina for both reaction processes (approximately 1 mol H(2) per kilowatt hour for dry reforming of methane and approximately 4.5 mol H(2) per kilowatt hour for direct decomposition of methanol).

Silver-Copper Oxide Heteronanostructures for the Plasmonic-Enhanced Photocatalytic Oxidation of N-Hexane in the Visible-NIR Range.

Volatile organic compounds (VOCs) are recognized as hazardous contributors to air pollution, precursors of multiple secondary byproducts, troposphere aerosols, and recognized contributors to respiratory and cancer-related issues in highly populated areas. Moreover, VOCs present in indoor environments represent a challenging issue that need to be addressed due to its increasing presence in nowadays society. Catalytic oxidation by noble metals represents the most effective but costly solution. The use of photocatalytic oxidation has become one of the most explored alternatives given the green and sustainable advantages of using solar light or low-consumption light emitting devices. Herein, we have tried to address the shortcomings of the most studied photocatalytic systems based on titania (TiO2) with limited response in the UV-range or alternatively the high recombination rates detected in other transition metal-based oxide systems. We have developed a silver-copper oxide heteronanostructure able to combine the plasmonic-enhanced properties of Ag nanostructures with the visible-light driven photoresponse of CuO nanoarchitectures. The entangled Ag-CuO heteronanostructure exhibits a broad absorption towards the visible-near infrared (NIR) range and achieves total photo-oxidation of n-hexane under irradiation with different light-emitting diodes (LEDs) specific wavelengths at temperatures below 180 °C and outperforming its thermal catalytic response or its silver-free CuO illuminated counterpart.